生信基本概念

Gene Ontology （GO）

在读懂基因本体论（Gene Ontology）前，我们先看看什么是本体论：

本体论（Ontology ）是探究世界的本原或基质的哲学理论 。

本体论通常处理的问题：存在哪些本质，如何将这些本质分组，在层次结构内关联以及如何根据相似性和差异进行细分 。

Ontology is the branch of philosophy that studies concepts such as existence, being, becoming, and reality. It includes the questions of how entities are grouped into basic categories and which of these entities exist on the most fundamental level.

基因本体论（Gene Ontology）包含生物学领域知识体系本质的表示形式，本体通常由一组类（或术语或概念）组成，它们之间具有关系。 基因本体论（GO）从三个方面（GO domains）描述了我们对生物学领域的了解：

1.分子功能（Molecular Function，MF ）
单个的基因产物（包括蛋白质和RNA）或多个基因产物的复合物在分子水平上的活动，比如“催化”，“转运”

需要注意，这里的描述只表示活动，而不指定执行功能的实体（分子或复合物），动作发生的地点，时间或背景

广义上的例子是催化活性和转运蛋白活性。具体的例子是腺苷酸环化酶活性或Toll样受体结合

为避免基因产物名称与其分子功能之间的混淆，GO分子功能通常附加“活性（activity）”一词。比如，蛋白激酶（protein kinase）具有GO分子功能：蛋白激酶活性（ protein kinase activity）

2.细胞组分（Cellular Component ，CC）
基因产物在执行功能时所处的细胞结构位置，比如在线粒体，核糖体

需要注意：细胞组分是细胞解刨结构，不指代过程

3.生物过程（Biological Process ，BP）
通过多种分子活动完成的生物学过程

广义上的例子是DNA修复或信号转导。更加具体的例子是嘧啶核苷生物合成过程或葡萄糖跨膜转运

需要注意：生物学过程不等同于通路。目前，GO没有表示完整的通路信息所需的动力学或依赖性的描述信息

理解了上述的概念，现在举个例子，如果站在基因本体论GO的角度来解释一个基因的话：

基因产物：细胞色素C（cytochrome c）

分子功能：氧化还原酶活性

细胞组分：线粒体基质

生物过程：氧化磷酸化

How do geneticists indicate the location of a gene?

Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene's position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome.

Cytogenetic location

Geneticists use a standardized way of describing a gene's cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome:

17q12

It can also be written as a range of bands, if less is known about the exact location:

17q12-q21

The combination of numbers and letters provide a gene's “address” on a chromosome. This address is made up of several parts:

• The chromosome on which the gene can be found. The first number or letter used to describe a gene's location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.

• The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene's address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.

• The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.

The CFTR gene is located on the long arm of chromosome 7 at position 7q31.2.

Credit: U.S. National Library of Medicine